The mouse has become the mainstay of genetic and cancer research, and mouse imaging has allowed scientists to monitor tumor development or remission serially. The combination of mu/PET, which provides functional biological information (e.g. tumor uptake, gene expression, etc.) with mu/CT techniques, which provides the anatomical context for the functional information, has proved to be a very important tool for this. However, the radiation dose associated with these procedures can be high, and this limits their frequent use. While the radiation does not harm the animal, it may affect immune response mechanisms and change the experimental outcome. We hypothesize that 2D images may be sufficient in some scientific applications to provide the biological information necessary, in lieu of 3D image data sets that mu/CT and mu/PET provide. In this application, we propose the development of a hybrid two-dimensional imaging system for the mouse and other small animals. This system uses 7-ray projection imaging combined with x-ray projection radiography, and we refer to this as MINX (mouse imaging using nuclides and x-rays). The MINX system uses a single computed radiography CR detector (BaFBr imaging plate) to capture both the 7-ray and x-ray images. We hypothesize that the MINX system will provide mouse researchers with information similar to mu/PET/mu/CT, however the reduced radiation dose and lower imaging costs will allow investigators to perform more imaging on the same animal and therefore collect serial data more frequently. The six Specific Aims include (1) Monte Carlo and numerical simulation studies to define the most optimal MINX system design, (2) the manufacture of a parallel hole collimator appropriate for mouse imaging using microlithography techniques, (3) the construction of the MINX system itself, (4) the development of appropriate phantoms followed by phantom imaging, (5) initial studies on mice for further optimization, and finally (6) serial analysis using the MINX system on mice simultaneous with mu/CT/mu/PET imaging for comparison. This study is designed to demonstrate the utility of fiducially aligned 2-D nuclear/x-ray projection images in mouse research, and we expect that the development of the MINX system will give mouse researchers another important tool for the assessment of biological function and genetic pathways.